Waching daily May 31 2017

There are over a billion people who smoke tobacco around the world, which makes it one

of the most popular psychoactive substances used in society.

The majority of tobacco users smoke cigarettes, but some smoke cigars or pipes, chew tobacco

or practice snuffing which is where ground up tobacco leaves are pushed up the nose.

Given the popularity of tobacco as well as its negative health consequences, it's considered

one of the leading causes of preventable death and disease worldwide.

Cigarette smoke contains over 4,000 toxic chemicals.

These toxins cause endothelial cell damage which creates inflammation along the inner

lining of arteries.

The inflammation increases the risk of having a myocardial infarction - a heart attack,

a stroke, and peripheral vascular disease which is where there is severe pain in the

lower legs.

The toxins can also cause pulmonary problems because the toxins get deposited into the

lungs, which damages the lung tissue and makes them more likely to get infected as well.

Finally, the cigarette smoke has a lot of different carcinogens, including ammonia,

formaldehyde, carbon monoxide, which are associated with cancers of the mouth, throat, lung, bladder,

pancreas, and uterus.

Combining these effects, a heavy smoker who smokes two packs of cigarettes each day, for

20 years, loses about 14 years of life.

Despite the negative consequences of smoking, most people continue to smoke because tobacco

contains nicotine, a tiny, fat-soluble molecule that creates pleasurable psychoactive effects

and is extremely addictive.

Nicotine is considered "responsible" for the high rates of tobacco dependence and addiction,

while the 4,000 other chemicals and compounds are "responsible" for the negative health

effects associated with smoking.

When a cigarette is lit, some of the nicotine gets destroyed by the heat, and some gets

into the smoke that gets inhaled.

As a result, smokers are able to "self-titrate" their nicotine dose by inhaling more frequently,

more deeply, or for a longer amount of time.

Once nicotine is absorbed into the bloodstream, it binds to a type of acetylcholine receptor,

called a nicotinic acetylcholine receptor - also called a nicotinic receptor - which

is found throughout the body and brain.

In the central nervous system, nicotinic receptors are on pre-synaptic axon terminals of neurons,

and when nicotine binds to them, it triggers the release of neurotransmitters like dopamine,

acetylcholine, and glutamate, which is why it's considered an acetylcholine agonist.

The psychoactive effects of nicotine are related to the locations of nicotinic receptors in

the brain and the exact neurotransmitters that are released when the receptors are stimulated.

For example, increased dopamine in the mesolimbic system, a reward pathway composed of the ventral

tegmentum and the nucleus accumbens causes pleasure, improved attention and mental processing,

and working memory.

Nicotine directly increases dopamine levels in the nucleus accumbens, but it also increases

glutamate levels which gets the ventral tegmentum neurons to release more dopamine onto the

nucleus accumbens.

Nicotine also decreasing the activity of inhibitory GABA neurons in the ventral tegmentum, so

by inhibiting the inhibitory neurons there's a double negative, which means that this is

one more way to create an increase in dopamine levels.

When nicotine binds to receptors in the peripheral nervous system, it increases blood pressure,

heart rate, cardiac contractility, and gastrointestinal tract activity.

Nicotine also binds to receptors on skeletal muscles causing relaxed muscle tone.

Over time, individuals who consistently use cigarettes can develop tolerance to the effects

of nicotine.

This means that with repeated use, they have a reduced response to nicotine, and therefore

an increased dose of nicotine is needed to achieve the original response.

At a cellular level, there are a couple theories that explain why this might happen.

One is that repeated exposure to nicotine may cause nicotinic receptors to become less

sensitive to nicotine.

Another theory is that neurons may remove nicotinic receptors from the cell wall in

a process called down-regulation, leaving fewer receptors available for binding.

In either scenario, tolerance leads to the need for higher and higher doses of nicotine

over time.

Let's step back for a moment - and say that you're at rest, without anything stimulating

your reward pathway.

In this situation, your brain keeps your heart rate, blood pressure, and wakefulness in a

normal state, called homeostasis.

Now, let's say that your secret crush sends you a text.

All of a sudden you may feel sweaty and flushed, your heart rate may jump a bit.

You're now above your normal level of homeostasis, because something has changed, right?

But it doesn't stay that way for long, and after the text, your brain brings things back

down to this baseline.

With repeated cigarette/tobacco use, a few things start to happen.

If you smoke at a specific time and setting, like on the porch at 6pm after dinner, and

being a stimulant, it makes everything speed up, including heart rate, blood pressure,

and wakefulness.

Your brain picks up on that pattern!

Next time, when you are on the porch at 6pm after dinner, your brain preemptively decreases

the heart rate, blood pressure, and wakefulness in an effort to create balance, because it

knows that when you smoke a cigarette, everything is going to increase.

Now, let's say that your 6pm after-dinner porch time rolls around, but you don't have

a cigarette.

In that situation, the brain still decreases heart rate and blood pressure, but the changes

aren't countered with the effects of nicotine, and so you might feel awful.

These awful feelings are called withdrawal symptoms.

Withdrawal symptoms can persist to the point where a person may need to smoke just to feel

normal.

Symptoms of nicotine withdrawal include severe craving for nicotine, irritability, anxiety,

anger, poor concentration, restlessness, impatience, increased appetite, weight gain, and insomnia.

Withdrawal symptoms can begin within 2 hours after the last use of tobacco, and typically

peak within 1 or 2 days.

While withdrawal tends to decline over the next few days and weeks, many smokers continue

to feel awful for months after their last cigarette.

The withdrawal symptoms associated with stopping smoking and the intense feelings of craving

make it very difficult to stop smoking - in fact, nearly 70% of those who smoke say that

they want to quit, and more than half of smokers try to quit each year, but of those, only

about 5% are successful.

The liver is quick to metabolize and eliminates nicotine from the body; in fact, it's half-life

is only about 1-2 hours.

To maintain the positive feelings that nicotine creates and avoid withdrawal, a person has

to smoke a cigarette every 2 hours or so, to reach a steady state of nicotine in the

blood - and that helps explain why individuals become chain smokers.

Also, at night, the liver eliminates the nicotine that has built up throughout the day, which

is why heavy smokers often need a cigarette first thing in the morning.

There are a number of different smoking cessation treatments.

Nicotine replacement therapies include nicotine-containing gum, lozenges, transdermal patches, nasal

sprays, inhalers, dissolvable tobacco, mouth sprays, and sublingual products.

These products are meant to help a person slowly taper their dose of nicotine and ultimately

quit altogether.

There are also medications that act on nicotinic receptors like buproprion and partial nicotine

receptor agonists like varenicline which help reduce withdrawal symptoms and prevent relapse.

Both of these can be used in conjunction with nicotine replacement medications and have

been shown to increase the success rates of individuals trying to quit tobacco.

Some smokers turn to electronic cigarettes, which are battery-powered devices that produce

a nicotine vapor that is inhaled.

Like some of the other nicotine replacement medications, they allowing smokers to go outside,

enjoy the feeling of holding a cigarette, and inhaling and exhaling a vapor.

Electronic cigarettes offer the same theoretical advantages of nicotine replacement, but unlike

nicotine replacement medications there's less research on the safety of e-cigarettes.

People trying to quit can also benefit from simple therapy interventions, for example,

simply asking a person about their willingness to quit, actually increases the likelihood

that they will quit.

Typically at clinic visits, it's recommended to ask about tobacco use, advise to quit or

cut back, assess whether a person is willing to quit, assist with quit attempts by offering

counseling and medications, and help arrange or organize a support network.

All right, as a quick recap, the nicotine in tobacco affects different neurotransmitters

and neural systems in the brain, which produces effects that are initially pleasant or enjoyable,

but can become more problematic and unpleasant if smoking continues over time.

Long-term use can cause tolerance, which is the need for increasing doses to achieve the

same effect, as well as dependence, which is the reliance on the tobacco/nicotine to

function normally.

The most effective treatments can include a combination of therapy and medications—with

a lot of love and support from family and friends.

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